chr11-47420702-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_ModeratePP5_Moderate
The NM_002804.5(PSMC3):c.910C>T(p.Arg304Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PSMC3
NM_002804.5 missense
NM_002804.5 missense
Scores
10
4
1
Clinical Significance
Conservation
PhyloP100: 2.47
Genes affected
PSMC3 (HGNC:9549): (proteasome 26S subunit, ATPase 3) The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes one of the ATPase subunits, a member of the triple-A family of ATPases that have chaperone-like activity. This subunit may compete with PSMC2 for binding to the HIV tat protein to regulate the interaction between the viral protein and the transcription complex. A pseudogene has been identified on chromosome 9. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, PSMC3
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.912
PP5
?
Variant 11-47420702-G-A is Pathogenic according to our data. Variant chr11-47420702-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1804031.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSMC3 | NM_002804.5 | c.910C>T | p.Arg304Trp | missense_variant | 9/12 | ENST00000298852.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSMC3 | ENST00000298852.8 | c.910C>T | p.Arg304Trp | missense_variant | 9/12 | 1 | NM_002804.5 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1405132Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 693660
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1405132
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
693660
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 NFE exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Patent ductus arteriosus;C0016522:Patent foramen ovale;C0265914:Abnormality of the pulmonary veins;C0266464:Polymicrogyria;C0344724:Atrial septal defect, ostium secundum type;C0557874:Global developmental delay;C1839546:Microretrognathia;C1840379:Cerebellar vermis hypoplasia;C2315100:Failure to thrive;C3276036:High anterior hairline;C4551563:Microcephaly;C4551649:Developmental dysplasia of the hip Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München | Apr 14, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
D;D;D;D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;.;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
Sift4G
Pathogenic
D;D;D;D;.
Polyphen
1.0
.;D;D;D;.
Vest4
MutPred
0.69
.;Loss of disorder (P = 0.0129);Loss of disorder (P = 0.0129);.;.;
MVP
MPC
2.3
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at